Loss of cushioning between joint surfaces is a basis of several significant orthopedic problems. Damage to contact surfaces in articular joints such as hips, shoulders, knees and digits as a consequence of arthritic conditions also results in debilitating disease which may require surgical intervention in the form of joint replacement with synthetic materials. Loss of cushioning between joint surfaces may also be the result of damage to tissues, such as ligaments, which stabilize joints, causing misalignment of articulating surfaces and resulting in abnormal wear. Such misalignment traditionally may require surgical intervention to stabilize the joint and re-establish normal joint articulation. Degeneration of intervertebral disc tissues results in chronic, debilitating back pain, calcification and rigidification of the spine and significant neurological consequences not only in humans but also in domestic animals, particularly dogs. Surgical alternatives include prosthetic devices to replace the intervertebral disc, some of which consist of metal/rubber artificial discs or synthetic hydrogels. For examples, see U.S. Pat. Nos. 5,879,396; 7,060,100; and 5,879,396.
Elastin, a natural structural protein, has received considerable attention for potential use in prostheses, such as vascular prosthesis, both in soluble forms for coating non-biological prostheses, and in solid forms to produce biologically-derived prostheses. Elastin has structural properties which make it suitable for use in prosthesis and it provides a biocompatible, non-thrombogenic surface for cell infiltration. It is a durable, extremely stable, and highly insoluble extracellular matrix protein which imparts the properties of extensibility and elastic recoil to tissues in which it is found, including large blood vessels, elastic ligaments, lung parenchyma, and skin.
Large arteries are a good source of elastin. Because human arteries are not available in quantity, animal arteries have been the primary source for elastin. However, arterial elastin is a highly insoluble matrix; therefore, soluble elastin-derived material is generated by treating the insoluble protein with acid or alkali, producing hydrolyzates such as alpha- and kappa-elastin. These are relatively undefined mixtures of peptides of mixed sizes. Thus, sources for large quantities of natural elastin are not readily available.
In attempts to develop biocompatible materials, soluble animal elastin materials have been used to coat non-biological prosthetic materials, usually with fixation by chemical cross-linking agents. For example, U.S. Pat. No. 4,960,423 (Smith) is directed to a synthetic vascular prosthesis coated with a water-soluble peptide derived from animal elastin.
U.S. Pat. No. 5,416,074 (Rabaud) is directed to a composition comprising elastin or a solubilized elastin peptide and another connective tissue protein, such as fibrin. The solubilized elastin peptide has a molecular weight of greater than 10,000.
U.S. Pat. No. 4,474,851 (Urry) is directed to an elastomeric composite material comprising an artificial core fiber, such as Dacron, and a polypeptide comprising repeating tetrapeptide or pentapeptide units. The units are derived from units observed to be repeated in the tropoelastin molecule, Val-Pro-Gly-Val-Gly (VPGVG; SEQ ID NO:6) and Val-Pro-Gly-Gly (VPGG; SEQ ID NO:7). The polypeptide comprises a series of beta-turns and is proposed to have a beta-coil structure. The polypeptide provides elastomeric properties to the composite material, but has little structural strength or integrity. The artificial core fiber provides these latter properties to the composite material.
U.S. Pat. No. 4,979,959 (Guire) is directed to a method of improving the biocompatibility of solid biomaterials by coating them with biocompatible agents and chemically linking the biocompatible agents to the surface via a photochemical reaction.
Elastin-based materials also have been used to produce solid materials from which prostheses can be manufactured. These include soluble animal elastin co-aggregated with other proteins such as collagen, fibrin, fibronectin and laminin, to produce gel-like materials, and polymerized materials derived from short hydrophobic sequences of human elastin (such as PGVGVA; SEQ ID NO:5). In some cases, these synthetic peptides also include short alanine-rich sequences containing lysine residues, allowing cross-linking between the elastin-like peptides or to other proteins such as collagen. Both elastin and collagen contain crosslinks derived from lysine. For example. U.S. Pat. No. 5,223,420 (Rabaud) is directed to an elastin-based product comprising an adduct containing elastin and at least one other protein, such as fibrin.
U.S. Pat. No. 4,589,882 (Urry) is directed to an artificial elastomeric copolymer comprising an elastomeric component of repeating units of tetrapeptides and pentapeptides and a crosslinking component which may comprise amino acid residues. The repeating units are derived from elastin. U.S. Pat. No. 4,132,746 (Urry) is directed to a synthetic, insoluble, crosslinked polypentapeptide. The pentapeptide is the VPGVG (SEQ ID NO:6) peptide present in tropoelastin. See also U.S. Pat. Nos. 4,500,700; 4,870,055, and 5,250,516 (all to Urry) for other materials derived from this peptide. The polypeptides described in these patents comprise a series of beta-turns and are proposed to have a beta-coil structure.
Animal arteries also have been stripped of extraneous material, leaving largely a matrix of elastin and collagen in tubular form that can be used for blood vessel replacement. For example, U.S. Pat. No. 4,776,853 (Klement) is directed towards a process for preparing an implantable biological material from suitable donor tissue.
U.S. Pat. Nos. 5,969,106; 6,489,446 and 6,765,086 describe polypeptides modeled on elastin and other naturally occurring fibrous proteins for use in a variety of applications, including as prosthesis (including vascular prosthesis), and in cosmetics.
There remains a need for synthetic polypeptide materials suitable for joint reconstruction, repair and cushioning that exhibit properties of extensibility, resilience and compressibility, yet are non-immunogenic and non-thrombogenic.